The objectives of this research project involve the search for biologically active constituents in the plant family Compositae. The work is particularly oriented toward the isolation and structure elucidation of cytotoxic and antineoplastic sesquiterpene lactones and acetylenic natural products from the subtribe Melampodiinae. Genera of this subtribe presently under investigation are: Melampodium, Clibadium, Desmanthodium, Polymnia, Calea and Tetragonatheca. Over 40 new sesquiterpene lactones have been isolated from the above genera, mainly from Melampodium. Separations of sesquiterpene lactones from active fractions have resulted in several anti-neoplastic compounds (Melampodin A acetate and Melampodinin). Major attention in our research is directed toward the structure-activity relationships in the natural and synthetically modified plant constituents, since anti-neoplastic activity of sesquiterpene lactones seems to depend not only on the presence of certain functional groups (alpha-methylene-gamma-lactones) but more importantly on the actual shape the lipophilicity and certain types of side chains (angelic acid, methacrylic acid) of these active principles.